The presence of a microsomal UDP-glucuronyl transferase for bilirubin in homozygous jaundiced Gunn rats and in the Crigler-Najjar syndrome.
The infusion of a closely related derivative of bilirubin, its dimethyl diester (DME), into jaundiced (jj) Gunn rats were associated with biliary excretion of mono- and diglucuronides of bilirubin. In vitro incubation of DME with liver microsomes from jj rats demonstrated sequential demethylation and glucuronidation of DME. Liver microsomes from a patient with the Crigler-Najjar syndrome were unable to form glucuronides of bilirubin in vitro unless DME was used as substrate. The results suggest that the deficiency in Gunn rats and in the Crigler-Najjar syndrome may be due to a structural defect in the microsomal matrix which contains glucuronyl transferase. This interpretation envisions a microenvironment of the transferase enzyme which is either impermeable to bilirubin or induces conformational changes which interfere with glucuronidation.
D000293:Adolescent; D000818:Animals; D001663:Bilirubin / Q000031:analogs & derivatives / Q000378:metabolism; D003414:Crigler-Najjar Syndrome / Q000201:enzymology*; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D006933:Hyperbilirubinemia, Hereditary / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011911:Rats, Gunn; D011919:Rats, Inbred Strains
C032217:bilirubin dimethyl ester; D014453:Glucuronosyltransferase; D001663:Bilirubin